1. Field of the Invention
The present invention relates to a medicament for preventive and/or therapeutic treatment of hyperphosphatemia. More specifically, the present invention relates to a medicament for preventive and/or therapeutic treatment of hyperphosphatemia which comprises a pharmaceutically acceptable anion exchange resin as an active ingredient.
2. Background Art
In patients of renal dysfunction, insufficiency of urinary phosphate excretion is observed. In the early stage of renal failure, a renal compensatory mechanism acts to keep phosphate homeostasis, and a temporary increase of phosphate excretion is observed due to the depression of phosphate re-absorption induced by the increase of PTH (parathyroid hormone). However, the homeostasis cannot be maintained because of progression of renal pathological conditions and renal hypofunction. As a result, hyperphosphatemia due to the decrease of phosphate excretion and a marked increase of PTH may arise. The accumulated phosphate causes, as direct actions, decrease of blood calcium, acceleration of PTH production/secretion, heterotopic calcification, and renal osteoparatrophy due to the depression of vitamin D activation. As indirect actions through high PTH level, it causes central and peripheral nervous disorders, myocardial disorders, hyperlipidemia, carbohydrate metabolic disorders, itch, dermal ischemic ulcer, anemia, tendon rupture, genital dysfunction, myopathy, growth retardation, cardiac conduction disturbance, pulmonary inflation disorder arterial sclerosis, and immune deficiency. In addition, it is also known that phosphate is an uremic substance and is involved directly or indirectly in complications of renal failure (Jin to Toseki, "Kidney and Dialysis", 37, 2:321, 1994).
When dialysis treatment is finally applied to patients of renal failure, the aforementioned pathologic conditions and complications are maintained, if homeostasis of phosphate cannot be sustained. Therefore, treatment of hyperphosphatemia is essential for patients of renal failure under or before the treatment of dialysis. For the treatments of hyperphosphatemia, 1) diet therapy, or 2) orally available phosphate adsorbent is currently applied.
Low protein food is used for the diet therapy. However, the effects of decrease of blood phosphate level are sometimes inefficient because its prolonged intake is limited and a certain level of protein intake cannot be avoided.
As orally available phosphate binders, mainly three types as set forth below are currently used. 1) Aluminum preparation (aluminum hydroxide): This preparation has problems of aluminum encephalopathy and aluminum osteopathy due to aluminum absorption. 2) Calcium preparation (calcium carbonate, calcium acetate): This preparation has weaker adsorbability compared to aluminum and requires higher dosage. In addition, there is also a problem that hypercalcemia may be caused due to calcium absorption. 3) Magnesium preparation (magnesium carbonate). This preparation has a problem that hypermagnesemia may be caused like the calcium preparation.
Therefore, each of the therapeutic treatments now available for hyperphosphatemia has the expected problematic actions, and cannot be applied for a prolonged period of time. Any improved therapeutic drug for hyperphosphatemia has not yet been discovered to date.
Japanese Patent Unexamined Publication (KOKAI) No. 56-150017/1981, European Patent Publication No. 98,884/A1, U.S. Pat. No. 4,412,011, and European Patent publication No. 157,410/A1 disclose that certain anion exchange resins have cholesterol-lowering activities. In addition, a cholesterol depressant comprising an anion exchange resin, i.e., cholestyramine resin, is sold by Bristol Myers Squibb Co. (trade name: Questran), and a cholesterol depressant comprising an anion exchange resin, i.e., colestipol hydrochloride, from The Upjohn Co. (trade name: Colestid). However, as far as the inventors of the present invention know, it has not reported to date that these anion exchange resins have phosphate ion-adsorbing activities, and furthermore, they have lowering activities on blood phosphate concentrations and reducing activities on urinary phosphate excretion.